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The mitochondrial succinate dehydrogenase complex subunit D (SDHD) is one of four proteins that make up the tricarboxylic cycle enzyme succinate dehydrogenase (SCH). Studies have shown that mutations in SDHD often leads to hereditary paragangliomas, usually benign tumors of the autonomic nervous system, suggesting that SDHD also plays a role as a tumor-suppressor gene. In one family with a nonsense mutation (R22X) in the SDHD gene, a loss of heterozygosity was found in the paragangliomas, and within these tumors the enzymatic activity of Complex II in the mitochondrial respiratory chain was completely abolished. Furthermore, high levels of angiogenic factors EPAS1 and VEGF was observed, which may stimulate tumor growth.
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